Program Booklet - Chemical and Biomolecular Engineering at the

Department of Chemical
& Biomolecular Engineering
PROUDLY PRESENTS THE
WINTER RESEARCH REVIEW
4TH YEAR TALKS
CLAYTON HALL
JANUARY 28, 2015
U N I V E R S I T Y o f D E L AWA R E
Department of Chemical
& Biomolecular Engineering
Alphabetical List of Talks
Matthew J. Armstrong, Advisors: Antony N. Beris and Norman J. Wagner
“Investigating the Thixotropic Behavior of a Concentrated Colloidal Suspension”
Committee: Eric M. Furst, Christopher J. Roberts, and James Tilton
Jennifer Au, Advisor: Maciek R. Antoniewicz
“Elucidation of Clostridium acetobutylicum Metabolism using Parallel Labeling Experiments and
13
C-Metabolic Flux Analysis”
Committee: Eleftherios T. Papoutsakis and Wilfred Chen
Gregory V. Barnett, Advisor: Christopher J. Roberts
“Specific Ion Effects on the Aggregation Mechanisms and Protein-Protein Interactions for
Anti-Streptavidin Immunoglobulin Gamma-1”
Committee: David W. Colby and Eric M. Furst
Qi Chen, Advisor: Wilfred Chen
“Engineering 3-Dimensional Protein Scaffolds for Biocatalysts Assembly”
Committee: April M. Kloxin and Kelvin H. Lee
Daniel Cook, Advisors: Raj Vadigepalli and Babatunde A. Ogunnaike
“Investigating Liver Regeneration Impaired by Cellular Adaptation to Chronic Diseases”
Committee: Maciek R. Antoniewicz, April M. Kloxin, and Anja Nohe
Colin D. Cwalina, Advisor: Norman J. Wagner
“The Shear-Thickened State in Concentrated Near Hard-Sphere Colloidal Dispersions”
Committee: Antony N. Beris and Eric M. Furst
Jingsi Gao, Advisor: Norman J. Wagner
“Colloidal and Nanoparticle Stability in Ionic Liquid [Bmim][BF 4 ] for Shear-Thickening Fluids (STFs) in Space”
Committee: Eric M. Furst, April M. Kloxin, and Mark B. Shiflett
Ke Gong, Advisor: Yushan Yan
“Redox Flow Batteries with a Double Ion-Exchange Membrane Design”
Committee: Richard Wool, Feng Jiao, Abraham M. Lenhoff, and Raul F. Lobo
Daniel Greene, Advisors: Abraham M. Lenhoff, Norman J. Wagner, and Stanley I. Sandler
“The Microstrucutre of Protein Precipitates”
Committee: Christopher J. Roberts and David W. Colby
Scott R. Horton, Advisor: Michael T. Klein
“Molecular-level Modeling of Municipal Solid Waste Gasification”
Committee: Dionisios G. Vlachos, Prasad Dhurjati, April M. Kloxin, and Frank Petrocelli
Bahar Ipek, Advisor: Raul F. Lobo
“Direct Methane Conversion to Methanol using Small-Pore Zeolites”
Committee: Yushan Yan, Dionisios G. Vlachos, Douglas J. Buttrey, and Craig M. Brown
Alphabetical List of Talks--Continued
Lilian Lam Josephson, Advisor: Eric M. Furst
“High-Throughput Passive Microrheology of Therapeutic Protein Solutions”
Committee: Abraham M. Lenhoff, Christopher J. Roberts, and Norman J. Wagner
Tyler Josephson, Advisors: Dionisios G. Vlachos and Stavros Caratzoulas
“Solvation Effects in Biomass Processing: Structure and Stability of 5-Hydroxymethylfurfural”
Committee: Michael T. Klein, Raul F. Lobo, and Stan I. Sandler
Jason A. Loiland, Advisor: Raul F. Lobo
“NO Oxidation Reaction Mechanisms over Microporous Materials”
Committee: Douglas J. Buttrey, Michael T. Klein, and Klaus H. Theopold
Robert J. Lovelett, Advisors: Babatunde A. Ogunnaike and Robert W. Birkmire
“High Throughput Production of High Efficiency Cu(InGa)(SeS) 2 Thin Film Solar Cells”
Committee: Raul F. Lobo and Antony N. Beris
Stephen Ma, Advisors: Christopher J. Kloxin and Norman J. Wagner
“Photodirected Wrinkle Formation through Click Chemistry”
Committee: April M. Kloxin and Xinqiao Jia
Eyas Mahmoud, Advisor: Raul F. Lobo
“Renewable Production of Aromatics from Biomass-Derived Furans”
Committee: Dionisios G. Vlachos, Donald A. Watson, and Paul J. Dauenhauer
Elizabeth G. Mahoney, Advisors: Jingguang G. Chen and Yushan Yan
“Designing Pt Monolayer Electrocatalysts for Fuel Oxidation in Alkaline Electrolytes”
Committee: Raul F. Lobo and Feng Jiao
Tyler Martin, Advisor: Arthi Jayaraman
“Theory and Simulation Studies of the Effect of Entropic and Enthalpic Driving Forces on Morphology in
Polymer Grafted Particle Filled Nanocomposites”
Committee at University of Colorado: C. Bowman, Y. Ding, J. Cha, and M. Glaser
Committee at University of Massachusetts - Amherst: R. Hayward
Olga Morozova, Advisor: David W. Colby
“Characterization and Detection of Misfolded Protein in Neurodegenerative Disease”
Committee: Christopher J. Roberts and Kelvin H. Lee
MyatNoeZin Myint, Advisor: Jingguang G. Chen
“Understanding the Reaction Pathways of C3 Oxygenates on Mo(110) and Co/Mo(110)”
Committee: Raul F. Lobo and Michael T. Klein
James Park, Advisors: Babatunde A. Ogunnaike, James Schwaber, and Rajanikanth Vadigepalli
“Molecular Plasticity of Single Cells in Disease Pathology”
Committee: David W. Colby and Abhyudai Singh
Alphabetical List of Talks--Continued
Jonathan Rosen, Advisor: Feng Jiao
“Mechanistic Insights into the Selective Conversion of CO 2 to CO on Precious and Non-Precious Metal Electrocatalysts”
Committee: Douglas J. Buttrey and Raul F. Lobo
Lisa A. Sawicki, Advisor: April M. Kloxin
“Tunable Hydrogels to Understand the Role of the Microenvironment in Regulating Breast Cancer Dormancy and
Recurrence”
Committee: Kelvin H. Lee, Wilfred Chen, and Millicent O. Sullivan
Amalie Tuerk, Advisor: Kelvin H. Lee
“Engineering- and Systems-based Approaches Enable Analysis of Proteins Involved in Chlorobaculum tepidum
Sulfur Metabolism”
Committee: Wilfred Chen, Thomas Hanson, April M. Kloxin, and Eleftherios T. Papoutsakis
Morgan A. Urello, Advisors: Millicent O. Sullivan and Kristi L. Kiick
“A CMP-based method for achieving Controlled, Cell-Responsive Delivery of DNA”
Committee: David W. Colby and April M. Kloxin
Jarrid A. Wittkopf, Advisor: Yushan Yan
“High-Performance Dealloyed PtCu/CuNW Oxygen Reduction Reaction Catalyst for Proton Exchange Membrane Fuel Cells”
Committee: Feng Jiao and Dionisios G. Vlachos
Mariah Woodroof, Advisor: Yushan Yan
“In-Situ Kinetic Studies of the Hydrogen Oxidation Reaction in Hydroxide Exchange Membrane Fuel Cells”
Committee: Feng Jiao, Abraham M. Lenhoff, Raul F. Lobo, and Richard Wool
Winter Research Review
John M. Clayton Hall
January 28, 2015
8:30-9:00
Breakfast (Clayton Hall lobby)
9:00-9:10
Welcome (Room 101 B)
Professor Abraham M. Lenhoff, Department Chair
Session 1 (Room 101 B) (9:10 a.m. – 10:30 a.m.)
9:10-9:30
9:30-9:50
9:50-10:10
10:10-10:30
10:30-10:50
Jason A. Loiland
“NO Oxidation Reaction Mechanisms over Microporous Materials”
Advisor: Raul F. Lobo / Committee: Douglas J. Buttrey, Michael T. Klein, and Klaus H. Theopold
Bahar Ipek
“Direct Methane Conversion to Methanol using Small-Pore Zeolites”
Advisor: Raul F. Lobo / Committee: Yushan Yan, Dionisios G. Vlachos, Douglas J. Buttrey, and
Craig M. Brown
Eyas Mahmoud
“Renewable Production of Aromatics from Biomass-Derived Furans”
Advisor: Raul F. Lobo / Committee: Dionisios G. Vlachos, Donald A. Watson, and
Paul J. Dauenhauer
Tyler Josephson
“Solvation Effects in Biomass Processing: Structure and Stability of 5-Hydroxymethylfurfural”
Advisors: Dionisios G. Vlachos and Stavros Caratzoulas / Committee: Michael T. Klein,
Raul F. Lobo, and Stan I. Sandler
Break & Poster Session
Session 2 (Room 101 B) (10:50 a.m. – 12:10 p.m.)
10:50-11:10
11:10-11:30
11:30-11:50
Elizabeth G. Mahoney
“Designing Pt Monolayer Electrocatalysts for Fuel Oxidation in Alkaline Electrolytes”
Advisors: Jingguang G. Chen and Yushan Yan / Committee: Raul F. Lobo and Feng Jiao
MyatNoeZin Myint
“Understanding the Reaction Pathways of C3 Oxygenates on Mo(110) and Co/Mo(110)”
Advisor: Jingguang G. Chen / Committee Raul F. Lobo and Michael T. Klein
Jonathan Rosen
“Mechanistic Insights into the Selective Conversion of CO 2 to CO on Precious and Non-Precious
Metal Electrocatalysts”
Advisor: Feng Jiao / Committee: Douglas J. Buttrey and Raul F. Lobo
Winter Research Review (cont’d.)
11:50-12:10
Robert J. Lovelett
12:10-1:30
Lunch (Room 101 A) and Featured Speaker, Feng Jiao
“High Throughput Production of High Efficiency Cu(InGa)(SeS) 2 Thin Film Solar Cells”
Advisors: Babatunde A. Ogunnaike and Robert W. Birkmire / Committee: Raul F. Lobo and
Antony N. Beris
Session 3 (Room 101 B) (1:30 p.m. – 2:50 p.m.)
1:30-1:50
1:50-2:10
2:10-2:30
Ke Gong
“Redox Flow Batteries with a Double Ion-Exchange Membrane Design”
Advisor: Yushan Yan/ Committee: Richard Wool, Feng Jiao, Abraham M. Lenhoff, and Raul F. Lobo
Mariah Woodroof
“In-Situ Kinetic Studies of the Hydrogen Oxidation Reaction in Hydroxide Exchange Membrane
Fuel Cells”
Advisor: Yushan Yan/ Committee: Feng Jiao, Abraham M. Lenhoff, Raul F. Lobo, and Richard Wool
Jarrid A. Wittkopf
“High-Performance Dealloyed PtCu/CuNW Oxygen Reduction Reaction Catalyst for
Proton Exchange Membrane Fuel Cells”
Advisor: Yushan Yan/ Committee: Feng Jiao and Dionisios G. Vlachos
2:30-2:50
Scott R. Horton
2:50-3:10
Break & Poster Session
“Molecular-level Modeling of Municipal Solid Waste Gasification”
Advisor: Michael T. Klein / Committee: Dionisios G. Vlachos, Prasad Dhurjati, April M. Kloxin,
and Frank Petrocelli
Session 4 (Room 101 B) (3:10 p.m. – 4:10 p.m.)
3:10-3:30
3:30-3:50
Daniel Cook
“Investigating Liver Regeneration Impaired by Cellular Adaptation to Chronic Diseases”
Advisors: Raj Vadigepalli and Babatunde A. Ogunnaike / Committee: Maciek R. Antoniewicz,
April M. Kloxin, and Anja Nohe
James Park
“Molecular Plasticity of Single Cells in Disease Pathology”
Advisor: Babatunde A. Ogunnaike, James Schwaber, and Rajanikanth Vadigepalli /
Committee: David W. Colby and Abhyudai Singh
Winter Research Review
John M. Clayton Hall
January 28, 2015
8:30-9:00
Breakfast (Clayton Hall lobby)
9:00-9:10
Welcome (Room 101 B)
Professor Abraham M. Lenhoff, Department Chair
Session 1 (Room 125) (9:10 a.m. – 10:30 a.m.)
9:10-9:30
9:30-9:50
9:50-10:10
Colin D. Cwalina
“The Shear-Thickened State in Concentrated Near Hard-Sphere Colloidal Dispersions”
Advisor: Norman J. Wagner/ Committee Antony N. Beris and Eric M. Furst
Jingsi Gao
“Colloidal and Nanoparticle Stability in Ionic Liquid [Bmim][BF 4 ] for S hear-Thickening
Fluids (STFs) in Space”
Advisor: Norman J. Wagner/ Committee: Eric M. Furst, April M. Kloxin, and Mark B. Shiflett
Matthew J. Armstrong
“Investigating the Thixotropic Behavior of a Concentrated Colloidal Suspension”
Advisors: Antony N. Beris and Norman J. Wagner/ Committee: Eric M. Furst, Christopher J. Roberts,
and James Tilton
10:10-10:30
Lilian Lam Josephson
10:30-10:50
Break & Poster Session
“High-Throughput Passive Microrheology of Therapeutic Protein Solutions”
Advisor: Eric M. Furst / Committee: Abraham M. Lenhoff, Christopher J. Roberts,
and Norman J. Wagner
Session 2 (Room 125) (10:50 a.m. – 12:10 p.m.)
10:50-11:10
11:10-11:30
Stephen Ma
“Photodirected Wrinkle Formation through Click Chemistry”
Advisor: Christopher J. Kloxin and Norman J. Wagner / Committee: April M. Kloxin and
Xinqiao Jia
Tyler Martin
“Theory and Simulation Studies of the Effect of Entropic and Enthalpic Driving Forces on
Morphology in Polymer Grafted Particle Filled Nanocomposites”
Advisor: Arthi Jayaraman / Committee at University of Colorado: C. Bowman, Y. Ding, J. Cha,
and M. Glaser/ Committee at University of Massachusetts - Amherst: R. Hayward
Winter Research Review (cont’d.)
11:30-11:50
Lisa A. Sawicki
“Tunable Hydrogels to Understand the Role of the Microenvironment in Regulating Breast Cancer
Dormancy and Recurrence”
Advisors: April M. Kloxin/ Committee: Kelvin H. Lee, Wilfred Chen, and Millicent O. Sullivan
11:50-12:10
Morgan A. Urello
12:10-1:30
Lunch (Room 101 A) and Featured Speaker, Feng Jiao
“A CMP-based method for achieving Controlled, Cell-Responsive Delivery of DNA”
Advisor: Millicent O. Sullivan and Kristi L. Kiick/ Committee: David W. Colby and April M. Kloxin
Session 3 (Room 125) (1:30 p.m. – 3:10 p.m.)
1:30-1:50
Qi Chen
1:50-2:10
Gregory V. Barnett
2:10-2:30
2:30-2:50
2:50-3:10
“Engineering 3-Dimensional Protein Scaffolds for Biocatalysts Assembly”
Advisor: Wilfred Chen/ Committee: April M. Kloxin and Kelvin H. Lee
“Specific Ion Effects on the Aggregation Mechanisms and Protein-Protein Interactions for
Anti-Streptavidin Immunoglobulin Gamma-1”
Advisor: Christopher J. Roberts/ Committee: David W. Colby and Eric M. Furst
Daniel Greene
“The Microstrucutre of Protein Precipitates”
Advisors: Abraham M. Lenhoff, Norman J. Wagner, and Stanley I. Sandler
Committee: Christopher J. Roberts and David W. Colby
Olga Morozova
“Characterization and Detection of Misfolded Protein in Neurodegenerative Disease”
Advisor: David W. Colby/ Committee: Christopher J. Roberts and Kelvin H. Lee
Break & Poster Session
Winter Research Review (cont’d.)
Session 4 (Room 125) (3:10 p.m. – 3:50 p.m.)
3:10-3:30
3:30-3:50
Amalie Tuerk
“Engineering- and Systems-based Approaches Enable Analysis of Proteins Involved in
Chlorobaculum tepidum Sulfur Metabolism”
Advisor: Kelvin H. Lee/ Committee: Wilfred Chen, Thomas Hanson, April M. Kloxin,
and Eleftherios T. Papoutsakis
Jennifer Au
“Elucidation of Clostridium acetobutylicum Metabolism using Parallel Labeling
Experiments and 13C-Metabolic Flux Analysis”
Advisor: Maciek R. Antoniewicz/ Committee: Eleftherios T. Papoutsakis and Wilfred Chen
2015 Winter Research Review - http://www.che.udel.edu/grad/4thYrResearchReview.html
John M. Clayton Hall - http://www.udel.edu/conf/newark.htm
Poster Presenters
Matthew Armstrong
“Dynamic Data-Driven Parameter Estimation of Nonlinear Models Based on a
Parallel Simulated Annealing Method”
Advisors: Antony Beris and Norman J. Wagner
Stefanie M. Berges
“Development of a Fluorescent Barcoding System for High-Throughput, SingleCell Analysis”
Advisor: David W. Colby
Long Chen
“Engineering Protein Scaffolds for Metabolic Pathway Flux Enhancement”
Advisor: Wilfred Chen
Rebecca Chen
“Binding Induced Prodrug Activation for Cancer Treatment”
Advisor: Wilfred Chen
Nikodimos Gebreselassie
“Co-Culture Flux Analysis: A Novel Approach”
Advisor: Maciek R. Antoniewicz
Melissa B. Gordon
“Dynamic Bonds in Covalent Adaptable Networks”
Advisors: Christopher J. Kloxin and Norman J. Wagner
Maura Koehle
"Catalytic Transformation of Biomass-Derived Compounds on Zeolites
Containing Lewis Acid Sites"
Advisor: Raul Lobo
Christopher Long
“Comprehensive Study of Metabolic Flux Rewiring in E. coli Knockout Strains”
Advisor: Maciek R. Antoniewicz
Jennifer Mantle
“An in vitro Blood-Brain Barrier Model Derived from Human Induced
Pluripotent Stem Cells to Study Drug Transport”
Advisor: Kelvin H. Lee
Alexander Mironenko
“Hydrogenolysis Mechanism of Furans to Alkylated Furans: Chemistry of Ring
Activation”
Advisor: Dionisios G. Vlachos
Erik V. Munsell
“Histone-Targeted Gene Delivery Scaffolds for Bone Regeneration”
Advisor: Millicent O. Sullivan
Paul M. Mwasame
“Development of a Microstructural Model for Thixotropy in Colloidal
Dispersions with Yield Stress Based on Population Balances”
Advisors: Antony N. Beris and Norman J. Wagner
Poster Presenters Continued
Ryan Patet
“Tuning the Acidity of Solid Acid Zeolite Catalysts”
Advisors: Stavros Caratzoulas and Dionisios G. Vlachos
Kaleigh Reno
“Synthesis and Characterization of Biobased Bisphenol A Alternatives from
Lignin”
Advisors: Richard Wool and Thomas H. Epps, III
Ellinor Schmidt
"Enhancing Microbial Product Yields Through Chemotropic Carbon Capture"
Advisor: Terry Papoutsakis
Edward P. Schreiner
“Properties of Molybdenum Supported on Low Acidity Zeolites for Catalytic
Dehydrogenation”
Advisor: Raul F. Lobo
Cameron Shelton
“Decoupling Substrate Surface Interactions in Block Polymer Thin Film SelfAssembly”
Advisor: Thomas H. Epps, III
Huibo Sheng
“Selective Hydrodeoxygenation of Furfural to 2-Methylfuran Using FeCu/Silica Catalyst”
Advisor: Raul F. Lobo
Kay Siu
“Design and Construction of Synthetic Extracellular Sensors using Split Inteins”
Advisor: Wilfred Chen
Megan Smithmyer
“Development of a Hydrogel in vitro Model for Investigation of Fibroblast
Activation”
Advisor: April Kloxin
Andrew Tibbits
“Leading the Charge in Photo-Crosslinked Thiol-Ene Ionomer Networks for
Fuel Cells”
Advisors: Christopher Kloxin and Yushan Yan
Yan Zhang
"In Situ Formation of Cobalt Oxide Nanocubanes as Efficient Oxygen Evolution
Catalyst"
Advisor: Feng Jiao
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Investigating the Thixotropic Behavior of a Concentrated Colloidal Suspension
Matthew J. Armstrong
Advisors: Antony N. Beris, Norman J. Wagner
Committee Members: Eric M. Furst, Christopher J. Roberts, James Tilton
Applying large amplitude oscillatory shear (LAOS) to complex fluids induces nonlinear
rheological responses that can be interpreted in terms of the underlying microstructure and its
dynamics by modeling. We demonstrate this for prototype concentrated colloidal suspensions
using three semi-empirical thixotropic models: two from the literature [1,2], and a new model,
significantly improving a previous one also developed here [3]. All three models are based on a
scalar internal structural parameter but differ in the level of complexity and number of model
parameters. We comprehensively test the models against new experimental data taken on a
model thixotropic suspension that was initially developed at KU Leuven [4]. A 2.9vol% fumed
silica in paraffin oil and poly-isobutylene (31wt%) [4] was formulated and its rheological
responses to steady shear, step-up, step-down, shear reversal, and, for the first time, LAOS, and
novel one-directional LAOS deformations, were measured. The experiments were performed on
a strain-controlled TA Instruments ARES-G2 rheometer. Modeling of this stress response with
the three thixotropic models yields information about the dynamics of the internal structural
order parameter. The respective model parameters were found using a recently developed
parallel simulated annealing global optimization algorithm [5]. While all the models were found
to be able to quantitatively fit the steady state experimental data, important quantitative and
qualitative differences were observed regarding the transient LAOS data. Flow reversals
occurring during the LAOS experiments are suspected to be the reason for the failure of models
based on scalar structural parameters in modeling these flows as they fail to account for flowinduced structural anisotropy. This is confirmed by contrasting those results to the success of the
models to predict novel one-directional LAOS experiments. These results show the limits of
applicability of currently available single scalar-parameter based thixotropy models and identify
areas for improvement in thixotropic concentrated soft colloidal suspension modeling.
References
[1] Jan Mewis and Norman J. Wagner, Colloidal Suspension Rheology, Cambridge Univ. Press,
2012.
[2] Paulo de Souza Mendes and Roney Thompson. Rheol. Acta (2013) 52:673-694.
[3] Ashutosh Mujumbdar, Antony N. Beris and Arthur B. Metzner. J. Non-Newtonian Fluid
Mech. 102 (2002) 157-178.
[4] Konrad Dullaert and Jan Mewis. Rheol. Acta (2005) 45: 23-32.
[5] Armstrong, M.J., Beris, A.N. and Wagner, N.J., “Dynamic Data-Driven Parameter
Estimation of Nonlinear Models Based on a Parallel Simulated Annealing Method,” submitted to
Computers in Chemical Engineering, Nov. 2014 Ms. Ref. No.: CACE-D-14-00579.
------------------------------------------------------------------------------------------------------- Winter Research Review 2015
Elucidation of Clostridium acetobutylicum Metabolism using Parallel Labeling Experiments
and 13C-Metabolic Flux Analysis
Jennifer Au
Advisor: Maciek R. Antoniewicz
Committee Members: Eleftherios T. Papoutsakis & Wilfred Chen
Due to their wide substrate range, solventogenic clostridia are seen as a promising class of
organisms for biofuel production.1 Clostridium acetobutylicum, a model organism, was
historically used for industrial-scale acetone-butanol-ethanol fermentation, and remains a
potential candidate for butanol and butyrate production today. However, although the
biochemistry of C. acetobutylicum has been extensively reviewed, the central metabolic
pathways have remained only partially resolved. Two recent reconstructions of genome-scale
models2,3 have proposed different mechanisms for the biosynthesis of α-ketoglutarate, the
precursor for glutamate, glutamine and proline. Initial stable-isotope labeling experiments and
qualitative 13C-isotopomer analysis have supported the idea of an incomplete tricarboxylic acid
(TCA) cycle and suggested a Re-stereospecificity for the citrate synthase reaction.4,5 Further
insights into the metabolism of C. acetobutylicum may guide future efforts aimed at the
metabolic engineering of this organism for biofuels production.
In this work, we have rigorously validated the metabolic network model of C. acetobutylicum.
Using parallel labeling experiments and 13C-metabolic flux analysis (13C-MFA), we
quantitatively elucidated the central carbon metabolism and amino acid metabolism. Contrary to
previously proposed hypotheses, we found that while the TCA cycle runs in the oxidative
direction, there is no notable flux between α-ketoglutarate and succinyl-CoA or succinate and
fumarate, and that the conversion of succinyl-CoA to succinate proceeds independently. Using
multiple 13C-labeled amino acid tracers, we additionally showed that there is no flux between
malate and oxaloacetate, and that there exists a metabolic cycle where carbon flows from
aspartate to threonine, serine, pyruvate, oxaloacetate, and back to aspartate. We also identified a
putative citramalate synthase gene that is the first step in isoleucine biosynthesis in this
organism. Using the validated metabolic network model, we evaluated C. acetobutylicum
metabolism under various levels of butanol and butyrate stress. The results from these analyses
provide the basis for ongoing work on improving the tolerance of this organism to these
fermentation products.
[1] Tracy BP et al. 2012. Curr Opin Biotechnol. 23(3):364-81
[2] Lee J et al. 2008. Appl Microbiol Biotechnol. 80(5):849-62.
[3] Senger RS, Papoutsakis ET. 2008. Biotechnol Bioeng. 101(5):1036-52.
[4] Amador-Noguez D et al. 2010. J Bacteriol. 192(17):4452-61.
[5] Crown SB et al. 2011. Biotechnol J. 6(3):300-5.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Specific Ion Effects on the Aggregation Mechanisms and Protein-Protein Interactions for
Anti-Streptavidin Immunoglobulin Gamma-1
Gregory V. Barnett
Advisor: Christopher J. Roberts
Committee Members: David W. Colby, Eric M. Furst
Non-native protein aggregation is common in the biopharmaceutical industry and jeopardizes
product shelf life, therapeutic efficacy, and patient safety. Here we investigate the role of
protein-protein interactions on the growth and morphology of IgG1 aggregates. Aggregation
mechanisms of anti-streptavidin IgG1 were determined as a function of pH and NaCl
concentration in 10mM acetate buffer and compared to previous work in 5mM citrate. IgG1
effective charge was measured using electrophoretic light scattering and net protein-protein
interactions were investigated via static light scattering. G22 correlated with the aggregation state
diagram and illustrates the role of electrostatic interactions mediating the aggregation
mechanism. Differential scanning calorimetry was used as a measure of conformational stability.
Results highlight the changes in IgG1 Fab or Fc midpoint of unfolding temperatures with pH and
the NaCl concentration. IgG1 stability changes drastically with pH, NaCl concentration and
buffer. We develop a parallel temperature initial rates method to investigate temperature
dependence on aggregation rates across pH, NaCl concentration and buffer formulations. Our
experimental approach indicates protein-protein interactions may be predictive of aggregate
mechanism and morphology. Finally, we illustrate how protein-solute interactions can be
quantified experimentally, and use this to directly show that acetate vs. citrate ions accumulate
differently near the protein surface.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Engineering 3-Dimensional Protein Scaffolds for Biocatalysts Assembly
Qi Chen
Advisor: Wilfred Chen
Committee Members: April Kloxin and Kelvin H. Lee
In nature, enzymes are often assembled into complex structures that are more effective than
individual enzymes in converting raw materials into useful products. Many biologically-derived
scaffolds have been used for single and multi-enzyme assembly and have shown increased
overall reaction rates in one- or two-dimensional configurations. Analogously, we hypothesize
that the use of three-dimensional scaffolds could further enhance the performance of
biocatalysts. The E2 core of the pyruvate dehydrogenase complex from Bacillus
stearothermophilus is a genetically-modifiable 60-mer protein nanocage that is thermally stable
at temperatures as high as 70°C. In this talk, we will discuss combining the E2 nanocage with a
thermophilic endoglucanase, CelA (monomeric, 42 kDa) from Clostridium thermocellum,
resulting an enzyme assembly that benefit from more enzymatically favorable high reaction
temperatures. To investigate the feasibility of applying this approach to bulkier and more
complex enzymes, tetrameric -galactosidase (116 kDa each monomer) was conjugated onto E2
nanocage and the functionality of the enzyme was confirmed. This E2-based approach offers a
flexible platform upon which multi-enzyme cascade reactions involving monomeric or more
complex enzymes can be assembled and studied at the nanoscale.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Investigating Liver Regeneration Impaired by Cellular Adaptation to Chronic Diseases
Daniel Cook
Advisor: Raj Vadigepalli and Babatunde Ogunnaike
Committee Members: Maciek Antoniewicz, April Kloxin, and Anja Nohe
Liver resection followed by regeneration is used to treat chronic liver diseases, with
patients regenerating sufficient liver mass for metabolic function. Patients requiring resection or
transplant, however, likely have multiple comorbidities impairing regeneration. These
comorbidities include chronic diseases and common pharmaceuticals and recreational drug use
(including alcohol abuse). Despite extensive study, the molecular mechanisms governing
comorbidity-impaired liver regeneration remain incompletely understood. As a result, there are
no robust predictors of liver regenerative capacity in patients undergoing liver resection.
Therefore our work seeks to address the problems of incomplete understanding and lack of
predictive markers for regenerative capacity by using computational modeling to connect
molecular regulation and liver tissue response to resection.
We developed a computational model of liver regeneration that takes into account
molecular regulation in hepatocytes contributing to regeneration and course-grained estimations
of non-parenchymal cell activation. Using this model, we predicted experimental liver
regeneration profiles across multiple species including mice, rats, and human patients by tuning a
single parameter empirically related to body mass. Additionally, we predicted the molecular
mechanisms governing impaired liver regeneration in multiple chronic disease conditions
impairing regeneration, including alcoholic steatohepatitis. Our results implicated nonparenchymal cells as important regulators of the regenerative ability of hepatocytes.
We therefore investigated non-parenchymal cell activation during liver regeneration in
healthy rats and diseased rats suffering from early-stage alcoholic steatohepatitis. We found that
non-parenchymal cells dynamically changed their activation states during regeneration and in
response to alcohol. Adaptation to chronic alcohol consumption increased populations of nonparenchymal cells impairing liver regeneration and decreased populations of non-parenchymal
cells positively contributing to liver regeneration.
We then extended our computational regeneration model to consider explicitly nonparenchymal cell activation states to identify the functional impact of altered balances of nonparenchymal cell activation states on regeneration phenotype. Based on model simulations, we
predicted that an increased anti-inflammatory (M2) population of Kupffer cells coupled with an
increased anti-proliferative population of hepatic stellate cells was sufficient to explain impaired
regeneration caused by chronic adaptation to alcohol.
Furthermore, our modeling approach that describes liver regeneration by incorporating
molecular regulation, cell activation states, and physiological tissue response provides a
framework to predict the regenerative potential of individual patients based on physiological
measurements, biomarkers, and model simulations and to predict novel treatments for
individualized patient care. In the future, we expect personalized tools like the one developed in
this work to be used as clinical tools, rationally informing doctors during patient treatment
decisions.
------------------------------------------------------------------------------------------------------- Winter Research Review 2015
The Shear-Thickened State in Concentrated Near Hard-Sphere Colloidal Dispersions
Colin D. Cwalina
Advisor: Norman J. Wagner
Committee Members: Antony N. Beris and Eric M. Furst
In the course of performing extra-vehicular activities (EVA), astronauts are exposed to the peril
of micrometeoroid and orbital debris (MMOD). While generally less than a centimeter in size,
these MMOD particles travel at velocities ranging from 1-15 km/s (2,000 – 30,000 mph) in lowearth orbit, rendering them highly energetic and a threat to puncture the textile layers protecting
the pressurized air bladder. When intercalated into the space between fibrils of a protective
textile, colloidal shear thickening fluids (STFs) have been shown to dramatically improve the
penetration resistance of textile fabrics to ballistic and puncture threats, and as such, they are
attractive candidates to enhance the MMOD resistance of EVA suits.
In the present talk, recent experimental investigations will be discussed that have further
elucidated the nature of the colloidal shear-thickened state. At high shear rates, we confirm the
existence of a well-defined colloidal shear-thickened state predicted from rigorous theory and
Stokesian dynamics simulations. We find that the colloidal shear-thickened state can be defined
by material properties—the shear viscosity and the first and second normal stress difference
coefficients for suspensions—that are independent of the shear rate and only a function of the
particle volume fraction. These measurements of the deviatoric stress in concentrated
dispersions provide strong additional support for the hydroclustered mechanism of shear
thickening. We further postulate and show that these material properties are consistent with
those measured in non-Brownian suspensions.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Colloidal and Nanoparticle Stability in Ionic Liquid [Bmim][BF4] for Shear-Thickening
Fluids (STFs) in Space
Jingsi Gao
Advisor: Norman J. Wagner
Committee Members: Eric M. Furst, April M. Kloxin, Mark B. Shiflett
Shear-thickening dispersions of colloidal particles in ionic liquids (ILs) are being developed for
possible use to improve the ballistic, puncture and abrasion resistance of space suits and
micrometeorite and orbital debris (MMOD) shielding for spacecraft. ILs are being considered
for the solvent phase of shear-thickening dispersions for space applications because of their
thermal stability and low volatility. However, this can be challenging because the high ionic
strength of ionic liquids screens the electrostatic stabilizing forces that are typically important for
dispersing particles in polar solvents. For example, previous simulations and experiments have
shown that the high ionic strength in ionic liquids effectively shields the electrostatic repulsion
between silica particles, leading to significant particle aggregation [1]. In this work we examine
the role of solvation forces and solvent structuring as a means to stabilize nanoparticles and
colloids in ionic liquids. In particular, we create stable silica dispersions up to 65 wt % in
[Bmim][BF4] by chemically coating the surface with 1H, 1H, 9H-hexadecafluoro-1-nonanol.
The particle suspensions are stable and exhibit shear-thickening behavior.
In this work we quantitatively test an unproven hypothesis in literature, namely that stabilization
of particles in the ionic liquid is a consequence of a solvation layer induced by specific solvation
interactions of the ionic liquid with the particle surface. A combination of techniques, including
rheology, dynamic light scattering, electron microscopy, and small angle neutron scattering
(SANS) are employed to determine the mechanism of colloidal stability. Based on these results,
we hypothesize a specific mechanism by which solvation layers forming around the surface of
the particles. These solvation layers are initiated by hydrogen bonds between anion [BF4]- and
the fluorinated group on the surface coating. Analysis of SANS spectra across a broad range of
particle concentrations is used to develop a quantitative model for the inter-particle interactions
including the thickness of the solvation layer. The solvation layer thickness is determined to be
around 5 nm at room temperature and is confirmed by independent rheology and dynamic light
scattering measurements.
[1] Ueno, K.; Inaba, A.; Kondoh, M.; Watanabe, M., Langmuir 2008, 24, (10), 5253-5259.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Redox flow batteries with a double ion-exchange membrane design
Ke Gong
Advisor: Yushan Yan
Committee Members: Richard Wool, Feng Jiao, Abraham Lenhoff, Raul Lobo
Due to the long serving life and flexible scalability, redox flow batteries (RFBs) are considered
as promising energy storage system for wind energy storage to cope with its intermittent nature.
The wide application of RFBs further requires high energy density and low cost of the system.
Current RFBs comprise single ion exchange membrane, which only allows the combination of
redox pairs in the same charge (e.g., all vanadium RFB, V3+/V2+ vs. VO 2 +/VO2+, with all positive
charged ions), and therefore leave a lot of promising redox pair combinations with mixed
charges useless. Different from the conventional single membrane configuration, we have
developed a new double-membrane triple-electrolyte concept that offers unprecedented freedom
in choosing the redox pairs with different charges and the pHs of the electrolytes [1-3].
Specifically, the double-membrane cell with one anion-exchange membrane (AEM), one cationexchange membrane (CEM), and a middle electrolyte in between can incorporate an anion redox
pair and cation redox pair, markedly expanding the range of chemistries usable in flow batteries.
Among various possible combinations, we have demonstrated three examples: 1) Zn-Ce flow
battery that offers a 3.1 V cell voltage, the highest for an aqueous flow battery; 2) S-Fe flow
battery that is very inexpensive because S and Fe are the 5th and 1st most produced element,
respectively; 3) Zn-Fe flow battery that has a high cell voltage (1.99 V), high performance (647
mW/cm2 peak power density), and low overall cost (less than $100/kWh).
[1] Shuang Gu, Ke Gong, Emily Z. Yan and Yushan Yan, A multiple ion-exchange
membrane design for redox flow batteries, Energy Environ. Sci., 2014, 7, 2986-2998
DOI: 10.1039/C4EE00165F
[2] Y.S. Yan, S. Gu, K. Gong, Double-membrane triple-electrolyte redox flow battery design,
Application No.: 13/918444, Publication date: 01/02/2014
[3] Y.S. Yan, S. Gu, K. Gong, Multiple-membrane multiple-electrolyte redox flow battery
design, Application No.: 13/918452, Publication date: 01/02/2014
------------------------------------------------------------------------------------------------------- Winter Research Review 2015
The Microstrucutre of Protein Precipitates
Daniel Greene
Advisor: Abraham Lenhoff, Norman Wagner, Stanley Sandler
Committee Members: Christopher Roberts, David Colby
Proteins exhibit a diverse range of dense phases encompassing dense liquid phases, crystals, gels,
aggregates, and precipitates. The physical properties of these dense phases ultimately depend on
their microstructure. Unfortunately, a priori prediction of the microstructure is hindered by the
complex nature of protein molecules, making experimental investigation imperative. While the
protein crystal structure is known to atomistic detail, the structure of other dense phases is less
well known. Current theories describing the thermodynamics of phase separation into noncrystalline dense phases, such as precipitates, implicitly assume the dense phase structure is
amorphous, but in light of colloidal simulations this assumption may not be valid. Our goal is to
better understand the structure of protein dense phases so that the thermodynamics and kinetics
of protein phase separation can be appropriately modeled and to develop structure–function
relations that can be used to tune the physical properties of the dense phase.
Using transmission electron microscopy (TEM), small-angle scattering (SAS) techniques, and
computational tools we study the microstructure of two protein dense phases: salted-out
precipitates of lysozyme and salted-out precipitates of ovalbumin. In both cases the precipitates
do not exhibit birefringence but eventually crystals nucleate and grow from both systems. In the
first case, lysozyme precipitates, we find that the precipitate structure is amorphous. However,
in the second case, we find that ovalbumin precipitates form core-shell structures of order several
microns in size and within the shell ovalbumin self-assembles into well-defined structures that
are 12 ± 3 nm thick as measured by TEM. Furthermore, using SAS, we show that within these
shell structures, ovalbumin packs in an ordered fashion as opposed to a disordered packing and
that scattering on length scales similar to the size of the molecule can be described using a
nanocrystalline model comprising of order 100 ovalbumin molecules.
Our studies illustrate that protein precipitate microstructure is complex and not always
amorphous. Studying the structure of these materials yields insight into their physical properties,
may lead to alternate crystallization pathways, and opens the door to a new class of selfassembled structures.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Molecular-level Modeling of Municipal Solid Waste Gasification
Scott Horton
Advisor: Michael Klein
Committee Members: Dion Vlachos, Prasad Dhurjati, April Kloxin, and Frank Petrocelli
In 2010, there was 250 million tons of municipal solid waste (MSW) in the United States.
Over half of this waste ended up in landfills which fail to recover the energy stored within MSW.
The most basic waste-to-energy technology is incineration. While this process recovers energy, it
also poses problems to the environment due to SO x , NO x , dioxin, and furan emissions. Plasmaarc gasification has nonstoichiometric amounts of oxygen and reduces the production of these
harmful oxygenates while recovering energy from waste via syngas production. Furthermore,
due to the extremely high temperatures of the plasma torch, the final by-product is a salable
glass-like slag. The objective of this study is to aid process design by developing a molecularlevel kinetics model of plasma-arc gasification.
The MSW is typically described at the lumped level, i.e., biomass, food waste, and
plastics. In the present work, each of these lumped components was described at the molecularlevel. Biomass was modeled as cellulose, hemicellulose, and lignin. The modeled plastics were
polyethylene, polyethylene terephthalate, and polyvinyl chloride. These feeds were all
represented at the molecular level using Flory statistics for nearly linear polymers and lattice
theory for lignin.
The feed stream was converted into a reaction network using an in-house software tool,
the Interactive Network Generator (INGen). There were two major categories of reactions:
devolatilization/pyrolysis and gasification. The major pyrolysis reaction families were thermal
cracking, decarboxylation, and decarbonylation. For gasification, the dominant reaction type was
reaction with oxygen. The generated reaction network was integrated and optimized with
literature data.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Direct Methane Conversion to Methanol using Small-Pore Zeolites
Bahar Ipek
Advisor: Raul F. Lobo
Committee Members: Yushan Yan, Dionisios G. Vlachos, Douglas J. Buttrey, Craig M. Brown
Direct and selective conversion of methane to methanol is a challenging reaction due to the
inherent stability of methane [1] and to the facile oxidation of methanol. Methane can be
converted to methanol on Cu-ZSM-5 and Cu- mordenite zeolites in a cyclic process [2-4], but the
highest reported yield is only 13µmol methanol/g zeolite [5]. The reactive copper species on CuZSM-5 has been found to be a mono-μ-oxo-dicopper complex ([Cu–O–Cu]2+) based on a
correlation between an absorption band at 22,700 cm-1 in UV–vis spectra [3,5] with methanol
produced and specific features in the resonance-enhanced Raman spectra [6] of the samples.
We have investigated the conversion of methane to methanol on copper (II)-exchanged smallpore (8-membered ring) zeolites: Cu-SSZ-13 (CHA), Cu-SSZ-16 (AFX) and Cu-SSZ-39 (AEI).
All the samples produced methanol with yields as high as 39 µmol methanol/g zeolite and
methanol/Cu ratios up to 0.09 (the largest reported to date). No evidence of mono-μ-oxodicopper species was found in the UV–vis spectra of Cu-SSZ-13, Cu-SSZ-16 and Cu-SSZ-39,
however extra-framework Cu—O vibrations that cannot be assigned to mono-μ-oxo-dicopper
species were detected in Raman spectra of Cu-SSZ-13 and Cu-SSZ-39 zeolites. This finding
suggests the presence of a reactive Cu x O y species different than the mono-μ-oxo-dicopper(II)
complex, with a structure that has yet to be identified.
References
1. Holmen, A., Catal. Today 142, 2 (2009).
2. Groothaert, M. H., Smeets, P. J., Sels, B. F., Jacobs, P. A., and Schoonheydt, R. A., J. Am.
Chem. Soc. 127, 1394 (2005)
3. Smeets, P. J., Groothaert, M. H., Schoonheydt, R. A., Catal. Today 110, 303 (2005)
4. Smeets, P. J., Hadt, R.G., Woertink, J. S., Vanelderen, P., Schoonheydt, R. A., Sels, B. F.,
and Solomon, E. I., J. Amer. Chem. Soc. 132, 14136 (2010)
5. Alayon, E. M., Nachtegaal, M., Ranocchiari, M., and van Bokhoven, J. A., Chem. Commun.,
48, 404 (2012)
6. Woertink, J. S., Smeets, P. J., Groothaert, M. H., Vance, M. A., Sels, B. F., Schoonheydt, R.
A., and Solomon, E. I., Proc. Natl. Acad. Sci. USA 106, 18908 (2009)
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
High-throughput passive microrheology of therapeutic protein solutions
Lilian Lam Josephson
Advisor: Eric M. Furst
Committee Members: Abraham M. Lenhoff, Christopher J. Roberts, Norman J. Wagner
A key challenge encountered in the current development of therapeutic protein solutions is the
need to measure their viscosity to identify a stable, syringeable formulations in a large
composition space. Commercially available techniques such as capillary viscometry and
rotational rheometers are frequently used, but require relatively large sample volumes. This
sample size requirement restricts the number of rheological measurements in the early
development stage when only small amounts of protein are typically available.
This talk will focus on characterizing the viscosity of protein therapeutics over a wide range of
compositions with a minimal amount of material. Microrheology techniques are powerful
methods to study scarce biomaterials [1]. We use multiple particle tracking (MPT) in
combination with microfluidic stickers to provide a high throughput sample processing platform
for protein therapeutics. This work examines the microviscosity of three monoclonal antibody
solutions at 10 sample compositions with temperatures ranging from 5 to 45°C. The protein
solutions exhibit Newtonian fluid behavior over a frequency range of 0.05 to 50 s-1, and do not
show evidence of further microstructure development due to protein-protein association. The
resulting viscosity-temperature dependence will be discussed on the basis of modified Arrhenius
formula.
[1]
K.M. Schultz & E.M. Furst. Soft Matter 8, 6198-6205, 2012.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Solvation Effects in Biomass Processing:
Structure and Stability of 5-Hydroxymethylfurfural
Tyler Josephson
Advisors: Dion Vlachos, Stavros Caratzoulas
Committee Members: Michael Klein, Raul Lobo, Stan Sandler
5-Hydroxymethylfurfural (HMF) is a promising platform-chemical for sustainable fuels
and plastics. A major issue in the production of HMF is the side reactions that lead to significant
loss of sugars and high cost. Use of polar aprotic solvents improves HMF yields from sugar
dehydration by preventing HMF side reactions, but the influence of solvent on the structure of
HMF is not fundamentally understood. In an effort to understand solvent effects on HMF
stability and yield, solvent-induced frequency shifts (SIFS) of the carbonyl stretching vibration
ν(C=O) of 5-hydroxymethylfurfural were measured in six protic and aprotic solvents. The
Gutmann Acceptor Number (AN), an empirical measure of Lewis acidity, was found to correlate
with the measured frequency shifts.
The SIFS were then investigated using ab initio electronic structure calculations, treating
the solvent implicitly and with an explicit solvent ligand interacting with the carbonyl. The
conductor polarizable continuum model (CPCM) solvation model predicted that ν(C=O) shifted
as a function of the dielectric constant, in agreement with the analytical predictions of the
Kirkwood-Bauer-Magat (KBM) theory for a dipole in a dielectric continuum, but in
disagreement with experimental ν(C=O). Experimental ν(C=O) were best predicted using gasphase complexes of HMF and explicit solvent ligand. NBO analysis and Bader’s Atoms in
Molecules theory were used to investigate the electronic structure and hydrogen bonding in these
complexes. SIFS arose from H-bonding interactions, as observed in delocalization of carbonyl
lone-pair electrons to H-bonding solvent σ*(X-H) orbitals, and in increased charge density and
decrease in local potential energy at the H-bond (3,-1) critical point in the charge density.
Consequently, by predicting the experimental SIFS and examining the electronic structure, we
find the first theoretical evidence for treating Gutmann’s solvent AN as a measure of solvent
Lewis acidity. The solvent effect on reactivity descriptors was also investigated. Strong electronwithdrawing solvents increase the proton affinity of HMF, predisposing it to reaction with acids,
and decrease the energy of its lowest unoccupied molecular orbital (LUMO), making HMF more
susceptible to nucleophilic attack.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
NO Oxidation Reaction Mechanisms Over Microporous Materials
Jason A. Loiland
Advisor: Raul F. Lobo
Committee Members: Douglas J. Buttrey, Michael T. Klein, Klaus H. Theopold
The catalytic NO oxidation is an industrially important reaction currently investigated in
the context of emissions control technologies to abate the release of nitrogen oxides (NOx),
particularly in the selective catalytic reduction of NOx with ammonia (NH3-SCR) using zeolite
catalysts. The kinetic importance of NO oxidation in SCR over zeolites is unclear and seems to
depend on the catalyst, as sometimes it has been implicated as the overall rate-determining step
(RDS) [1], while in others cases it has been shown to not be the RDS [2]. Verma et al. [3] have
shown that NO oxidation can be a useful probe reaction for better understanding of the SCR
process.
NO oxidation rates were measured as a function of temperature from 298-623 K over H-,
Na-, and siliceous CHA materials to observe the effects that aluminum atoms and the extraframework cation (H+, Na+) have on reactivity. The materials exhibit two reaction regimes as a
function of temperature. Below a temperature of approximately 423 K, all materials display
substantial catalytic reactivity and reaction rates decrease with increasing temperature, resulting
in negative apparent activation energies (-24.9 to -37.5 kJ mol-1). The catalytic rates at low
temperatures are attributed to a confinement effect in the materials’ micropores that accelerate a
homogeneous-like reaction by stabilizing a N2O4‡ transition state inside the zeolite crystals [4].
The trend with temperature changes above 423 K, and reaction rates over H-SSZ-13 and NaSSZ-13 increase with increasing temperature [5], a clear indication that a different reaction
mechanism occurs above 423 K. The reaction rates over siliceous CHA are low and unaffected
by temperature above 423 K, indicating that the material has minimal catalytic activity in this
temperature window and that framework aluminum atoms with exchanged cations are necessary
to observe activity. In-situ FTIR studies reveal that NO+ is the only observable NxOy species
present in measurable concentrations on the alumino-silicate zeolites at high temperatures, and
we have proposed plausible mechanisms for the formation of NO+ at framework aluminum
positions within the zeolite pores.
The results presented in this report show the occurrence of two reaction regimes for the
oxidation of NO over H- and Na-zeolites: activity increases with decreasing temperature below
423 K, and activity increases with increasing temperature above 423 K. We have quantified, for
the first time, the contribution of acid sites to NO oxidation rates at SCR-relevant temperatures
and pressures. We also show that NO+ is in equilibrium with gas phase NO, and desorbs (as NO)
leaving behind an oxidized acid site (Si–O•–Al).
References
1. Metkar, P.S.; Balakotaiah, V.; Harold, M.P. Catal. Today 184, (2012) 115.
2. Kwak, J.H.; Tran, D.H.; Szanyi, J.; Peden, C.H.F.; Lee, J.H. Catal. Lett. 142, (2012) 295.
3. Verma, A.A.; Bates, S.A.; Anggara, T.; Paolucci, C.; Parekh, A.A.; Kamasamudram, K.;
Yezerets, A.; Miller, J.T.; Schneider, W.N.; Ribeiro, F.H. J. Catal. 312, (2014) 179.
4. Loiland, J.A.; Lobo, R.F. J. Catal. 311, (2014) 412.
5. Loiland, J.A.; Lobo, R.F. Submitted to J.Catal.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
High throughput production of high efficiency Cu(InGa)(SeS) 2 thin film solar cells
Robert J. Lovelett
Advisors: Babatunde A. Ogunnaike, Robert W. Birkmire
Committee Members: Raul Lobo, Antony Beris
Cu(InGa)(SeS) 2 (CIGSS) is a polycrystalline material used as the absorber in thin film
solar cells. CIGSS-based cells have high efficiency and stability, and are in the early stages of
commercialization. However, the leading process for producing CIGSS films is limited by long
reaction times and low throughput. This process, called the precursor reaction method, consists
of deposition of a Cu-In-Ga precursor followed by reaction in H 2 Se and H 2 S. Alternatively, a
Se-capping layer can be deposited on the CIG precursor and annealed in H 2 S to produce CIGSS.
CIGSS is a continuous solid solution of CuInSe 2 , CuGaSe 2 , CuInS 2 , and CuGaS 2 , and its
optical and electronic properties can be tuned by adjusting the Ga/(In+Ga) and S/(Se+S) ratios.
The kinetics and transport phenomena that control film growth provide opportunities to engineer
desirable characteristics. For example, the kinetics dictate that CuInSe 2 is produced faster than
CuGaSe 2 , leading to a gradient in the through-film composition and material properties.
However, we do not yet have a thorough understanding of the reaction mechanisms and diffusion
effects and cannot quantitatively predict the film structure with varying process conditions.
The overall goal of this project is to develop a fast and scalable process to produce
CIGSS thin films with the precursor reaction method. The three specific aims are: (1) to design
and deploy an rapid thermal processing (RTP) reactor; (2) to understand, via experiment and
simulation, the kinetics and transport phenomena that govern CIGSS synthesis; and (3) to
produce high efficiency CIGSS-based solar cells.
Reactor Design: The RTP reactor used in this study consists of a quartz tube with
graphite sample holder heated from above by a quartz-halogen lamp, and with temperature
measured by a pyrometer mounted below. H 2 Se, H 2 S and Ar cylinders deliver process gases for
reaction. To overcome a key challenge of measuring surface temperature (i.e., the temperature of
the reacting thin film), we designed and implemented a state estimator based on a first-principles
model and used it to provide real-time estimates of surface temperature. Furthermore, a
controller was designed to achieve the rapid temperature ramps required for this work.
Characterization and Simulation: The RTP reactor has been used to produce CIGSS
films under varying operating conditions, such as time, temperature, gas concentrations, and
precursor structure. The composition is measured by energy dispersive x-ray spectroscopy and xray fluorescence spectroscopy and the phase composition is determined by x-ray diffraction.
We are currently developing a stochastic model to simulate the reaction kinetics and
diffusion during CIGSS formation. The time evolution of through-film composition is predicted
from a model of a subset of solid-state reaction and diffusion events. Even though preliminary
results show material gradients consistent with experimental observations, we are refining the
model parameters to improve the model’s accuracy.
Solar Cell Production: Complete solar cells have been fabricated from precursors with
and without Se-capping layers and under varying process conditions. To date, the best efficiency
obtained is 12.9%. In future, we will employ the models we are developing to determine ideal
operating conditions and then use empirical optimization techniques to produce devices with the
highest efficiency.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Photodirected Wrinkle Formation Through Click Chemistry
Stephen Ma
Advisor: Dr. Christopher J. Kloxin and Dr. Norman J. Wagner
Committee Members: Dr. April M. Kloxin and Dr. Xinqiao Jia
Material wrinkling/buckling on an elastomer is a cost effective method to generate long range
surface topography and has led to numerous proposed applications ranging from antifouling
coatings,1, 2 tunable microarray lenses/optical coatings,3, 4 enhancements in solar cell efficiency,5,
6
and substrates for directed cell growth.7, 8 Despite a large body of work in this area, however,
the precise control over wrinkle confinement and orientation necessary to engineering textured
surface remains a challenge.
Photopolymerizable click chemistry offers an attractive new medium to spatiotemporally direct
wrinkle formation.9 To generate wrinkles, a base elastomer, embedded with photoinitiator and
photoabsorber, is formed using off-stoichiometric amounts of thiols and enes through Michael
type addition. The elastomer is then strained and irradiated with UV light to induce a second
polymerization of the excess functional groups. While the photoinitiator initiates the second
polymerization, the photoabsorber confines the UV light to a thin skin layer, creating the
necessary conditions for the wrinkle formation upon release of the strain. Through photomasked
UV light, these wrinkles can be selectively confined and oriented, facilitating the formation of
complex patterns with multiple distinct wavelengths as well as the formation of gradients
containing a continuum of wrinkle wavelengths. Current work includes design and synthesis of
new multi-functional monomers capable of undergoing orthogonal click chemistries, allowing
wrinkle formation under ambient conditions. With the wide selection of commercially available
and synthesizable monomers, photoinitiators, photomasks and stoichiometric control, we present
an alternative system to wrinkle formation that is highly versatile, further enabling the a priori
design and engineering of textured surfaces.
References:
(1) Efimenko, K., Finlay, J., Callow, M. E., Callow, J. A. and Genzer, J. ACS Appl. Mater.
Interfaces 2009, 1, 1031-1040
(2) Efimenko, K., Rackaitis, M., Manias, E., Vaziri, A., Mahadevan, L. and Genzer, J. Nature
Mater. 2005, 4, 293-297
(3) 251912 Chandra, D., Yang, S. and Lin, P.-C. Appl. Phys. Lett. 2007, 91,
(4) van den Ende, D., Kamminga, J. D., Boersma, A., Andritsch, T. and Steeneken, P. G. Adv
Mater 2013, 25, 3438-3442
(5) Kim, J. B., Kim, P., Pegard, N. C., Oh, S. J., Kagan, C. R., Fleischer, J. W., Stone, H. A. and
Loo, Y. L. Nat Photonics 2012, 6, 327-332
(6) Xie, K. Y. and Wei, B. Q. Adv Mater 2014, 26, 3592-3617
(7) Guvendiren, M. and Burdick, J. A. The control of stem cell morphology and differentiation by
hydrogel surface wrinkles 2010, 31, 6511-6518
(8) Guvendiren, M. and Burdick, J. A. Stem Cell Response to Spatially and Temporally
Displayed and Reversible Surface Topography 2013, 2, 155-164
(9) Ma, S. J., Mannino, S. J., Wagner, N. J. and Kloxin, C. J. Macro Letters 2013, 2, 474-477
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Renewable Production of Aromatics from Biomass-Derived Furans
Eyas Mahmoud
Advisor: Raul F. Lobo
Committee Members: Dionisios G. Vlachos, Donald A. Watson, Paul J. Dauenhauer
The selective conversion of renewable biomass feedstocks such as lignocellulose into
fuels and chemicals is of interest to reduce our dependence on fossil fuels and to decrease the
emission of anthropogenic greenhouse gases. One of the five major building blocks of the
chemical industry, aromatic species, cannot be produced from shale gas because most of the gas
has molecules with carbon numbers < 5. For example, one such aromatic molecule is phthalic
anhydride. More than three million tonnes of phthalic anhydride are manufactured worldwide
for the production of paints, plasticizers, and fabrics. We have investigated the conversion of
furan, a high-yield hemicellulose-derived species (86-95% overall yield from corn-stover), into
aromatics by the Diels-Alder cycloaddition followed by dehydration as a mechanism to generate
these species.
A barrier to the use of furan is its reactivity to Brønsted acids. To overcome this
limitation, we have developed a two-step reaction procedure to produce aromatics (scheme 1).
The low selectivity of the dehydration to the desired products was obviated by using binary
mixtures of methanesulfonic acid (MSA) and acetic anhydride for ether bond cleavage. We have
applied this methodology for the production of phthalic anhydride and benzoic acid.
Phthalic anhydride was produced in 96% yield after 4 h under solvent-free conditions by
the Diels–Alder reaction between furan and maleic-anhydride initially at 298 K. This reaction is
resistant to thermal runaway because of its reversibility and exothermicity. Subsequent
dehydration of the oxanorbornene was investigated using binary mixtures of MSA and acetic
anhydride. An 80% selectivity to phthalic anhydride (87% selectivity to phthalic anhydride and
phthalic acid) was obtained after running the reaction for 2 h at 298 K to form a stable
intermediate followed by 4 h at 353 K to drive the reaction to completion. This result is much
better than the 11% selectivity obtained in neat MSA using similar reaction conditions.
A second aromatic molecule of interest is benzoic acid. Benzoic acid, a commodity
chemical with applications in therapeutic drugs, food and industrial preservatives, plasticizers,
and fibers is currently produced at a 130,000 mt/year capacity in North America. Benzoic acid is
a platform molecule because it can be industrially converted to polystyrenes, polycarbonates, and
Nylon 6. Using quantitative nuclear-magnetic resonance (qNMR) spectroscopy we have shown
that Lewis-acid Hf-containing zeolite beta quantitatively catalyzes the Diels-Alder reaction of
methyl acrylate and furan acid to oxanorbornene carboxylic methyl ester at a turnover rate of 3.7
h-1 at 308 K. This species was subsequently dehydrated to produce benzoic acid in 96%
selectivity in binary mixtures of MSA and acetic anhydride, containing acetyl methanesulfonate.
Scheme 1. Two step reaction sequence for the conversion of furan to aromatics
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Designing Pt Monolayer Electrocatalysts for Fuel Oxidation in Alkaline Electrolytes
Elizabeth G. Mahoney
Advisors: Dr. Jingguang Chen and Dr. Yushan Yan
Committee Members: Dr. Raul Lobo and Dr. Feng Jiao
With the rising concern of climate change, an increasing amount of research has been
applied to improving sources of renewable energy. Electrochemical power sources such as fuel
cells have been cited as promising replacements for combustion-based technologies due to their
high efficiencies and power densities. The advent of proton exchange membranes warranted the
development of solid state fuel cells that boasted CO2-free exhaust from the oxidation of
hydrogen gas. However, proton exchange membrane fuel cells have encountered obstacles in
their commercial application due to the difficulty of producing hydrogen from environmentallyfriendly sources, the lack of efficient hydrogen storage systems, and the prohibitive cost and
scarcity of platinum (Pt) electrocatalysts. New systems have been explored that exploit
hydrocarbon fuels such as ethylene glycol, which can be produced from CO2-neutral feedstocks,
but the economic problems posed by the requirement of platinum catalysts in acidic media
remain a limiting factor.
One way to decrease the cost of fuel cells is to transition to an alkaline environment by
utilizing hydroxide exchange membranes instead of proton exchange membranes. So called
hydroxide exchange membrane fuel cells (HEMFCs) allow a wider range of catalytic materials
due to the high operating pH, which encourages the minimization or even eradication of Pt group
metal catalysts in the fuel cell. However, even on Pt, the activity of the hydrogen oxidation
reaction (HOR) is approximately two orders of magnitude slower in alkaline environments
relative to acidic environments. The reason behind this drop in activity has thus far been disputed
in literature. Besides the expected decrease in Pt activity expected when transitioning to an
alkaline environment, Pt is an expensive catalyst and a cheaper catalyst would greatly lower the
cost associated with HEMFCs. To decrease the catalyst cost, we determined the kinetic activity
of the alkaline HOR using a monolayer of platinum deposited on gold substrates (Pt ML/Au and
Pt ML/Au/C). The activity of Pt ML/Au and Pt ML/Au/C were shown to be similar to bulk Pt
and far higher than bulk Au. Preliminary work using Pt alloys has indicated there may be a role
of adsorbed hydroxyl in the alkaline HOR mechanism.
The lack of infrastructure for hydrogen storage and transportation currently limits the
practicality of using hydrogen as a fuel source. Nevertheless, HEMFCs also have the benefit of
functioning with alternative CO2-neutral feedstocks such as ethylene glycol and glucose. The
activities toward the alkaline oxidation of ethylene glycol and glucose were determined for Pt
ML/Au catalysts. In addition, the stability of each catalyst was compared to bulk Pt and Au. The
Pt ML/Au catalysts were found to have similar activity as bulk Pt as well as improved stability.
In order to determine the reaction intermediates and products for both the oxidation of ethylene
glycol and glucose, in-situ FTIR was used for the Pt ML/Au, Pt, and Au surfaces.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Theory and Simulation Studies of the Effect of Entropic and Enthalpic Driving Forces on
Morphology in Polymer Grafted Particle Filled Nanocomposites
Tyler Martin
Advisor: Prof. Arthi Jayaraman
Committee Members at University of Colorado: C. Bowman, Y. Ding, J. Cha, M. Glaser
Committee Members at University of Massachusetts - Amherst: R. Hayward
Polymer nanocomposites (PNC) are a class of materials that consist of a polymer matrix
embedded with nanoscale fillers or additives that enhance the overall composite properties. To
engineer PNCs for various applications (e.g. photovoltaics, optics, photonics, automobile parts,
etc.) with target macroscopic properties we need to relate molecular features of the polymers and
fillers to the PNC morphology and understand the thermodynamic driving forces underlying this
relationship. My thesis has been focused on PNCs comprised of polymer grafted particles as
fillers in a homopolymer matrix, with the overarching goal to tailor grafted polymer design for
achieving controlled dispersion and aggregation of particles in the matrix. The initial focus has
been on chemically identical graft and matrix polymers where we found that increasing the
polydispersity in grafted chain lengths [1-3] stabilizes the dispersion of particles within the PNC.
This is due to polydispersity increased wetting of the grafted layer by matrix chains due to
reduced conformational entropy loss upon wetting. We also found that decreasing flexibility of
the graft and matrix polymer stabilizes particle dispersion, due to increased wetting driven by
increased graft/matrix mixing entropy [4]. Our current focus is on chemically different graft and
matrix polymers, to tune enthalpic driving forces in addition to the entropic driving forces for
particle dispersion/aggregation. Specifically, we study systems of graft and matrix random
copolymers that have a Flory Huggins χ parameter that becomes increasingly negative with
inverse temperature, thus exhibiting mixing at low temperatures and phase separation at higher
temperatures (or lower critical solution temperature, LCST, behavior). Our work is partly
motivated by Hayward and coworkers [5], who created PNCs with LCST thermo-reversible
aggregation-dispersion behavior via the use of hydrogen bond donors and acceptors in the graft
and matrix random copolymer chains. Our goal is to predict how this aggregation/dispersion
transition of grafted nanoparticle filled PNCs changes with filler fraction, grafting density,
particle size, graft and matrix random copolymer length and composition, and to compare to
phase behavior of graft and matrix polymer blend without nanoparticles (ungrafted blends).
Using coarse-grained molecular dynamics simulations [2,4], we identify the
aggregation/dispersion phase transition using particle-particle structure factors as a function of
filler fraction, grafting density and graft/matrix composition, and characterize the order of phase
transition to be first order. The aggregation/dispersion phase transition for the grafted systems is
at a lower temperature than the mixing/demixing phase transition of ungrafted blends. Grafting
density does not strongly affect the location of the phase boundary, although it does slightly
affect its shape. The wetting/dewetting transition of the grafted layer by matrix chains begins at a
higher temperature and preceeds the aggregation/dispersion transition. While the
aggregation/dispersion transition is a first order phase transition, the wetting/dewetting transition
appears to be a second order phase transition. All of the above results and underlying
mechanisms positively impact the polymers community by providing valuable design rules to
engineer PNC with precise phase behavior.
1) Martin, T. B.; Dodd, P. M.; Jayaraman, A.,. Phys. Rev. Lett. 2013, 110 (1), 018301., 2)Martin, T. B.; Jayaraman,
A., Soft Matter 2013., 9 (29), 6876-6889 .3) Martin, T. B.; Jayaraman, A., Macromolecules 2013, 46 (22), 91449150. 4) Lin, B.; Martin, T. B.; Jayaraman, A., ACS Macro Lett 2014, 3 (7), 628-632., 5) Heo, K.; Miesch, C.;
Emrick, T.; Hayward, R. C.. Nano Lett. 2013, 13 (11), 5297-5302.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Characterization and Detection of Misfolded Protein in Neurodegenerative Disease
Olga Morozova
Advisor: David Colby
Committee Members: Christopher Roberts, Kelvin Lee
Fibrils composed of tau protein are a pathological hallmark of several neurodegenerative
disorders including Alzheimer’s disease (AD) and other tauopathies such as corticobasal
degeneration (CBD), progressive supranuclear palsy (PSP), and Pick’s disease (PiD). In disease
brain tissue, misfolded tau fibril conformations are distinct for different tauopathies. Insight into
the propagation of these structures will allow us to study the spread of tau fibrillization through
the brain and improve the specificity of early tauopathy detection. Based on the evidence that tau
fibrillization propagates specific conformations with seeding, we created a biochemical model
for structural analysis of misfolded tau conformations from human tissues. We show that when
recombinant tau protein is seeded with fibrils isolated from AD and tauopathy brains, the
amyloid formed shares many of the structural features of tauopathy fibrils. Our results suggest
that disease-specific fibrils act as a conformational template for the formation of recombinant tau
fibrils. To assess the conformation of tau in cerebrospinal fluid (CSF), we implemented a
biochemical seeding assay that sensitively detects misfolded tau protein by monitoring the rate of
conversion of recombinant tau protein into an amyloid conformation. Amyloidogenic tau was
found in CSF samples obtained from individuals with AD, CBD, and PSP, but not in samples
obtained from age-matched controls. Seeding with misfolded tau conformations found in CSF
from patients with different diseases propagated distinct conformations of recombinant tau
fibrils. Although CSF biomarkers for AD have been reported to be 90% sensitive, widely
accepted biomarkers for other tauopathies are unavailable. Our findings suggest a possible
biomarker directly linked to tau pathology and support the possibility of prion-like propagation
of tau deposits between neurons in AD and other neurodegenerative diseases.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Understanding the Reaction Pathways of C3 Oxygenates on Mo(110) and Co/Mo(110)
MyatNoeZin Myint
Advisor: Jingguang G. Chen
Committee Members: Raul F. Lobo, Michael T. Klein
The reactions of biomass-derived oxygenates on transition metal surfaces have been of
particular interest in the field of heterogeneous catalysis as a promising way to produce valueadded fuels and chemicals from renewable sources.1 Catalytic transformation of oxygenates,
particularly the most commonly studied alcohols and aldehydes,2 includes but not limited to
C‒O/C=O bond scission to produce alkenes via deoxygenation, and C‒C and C‒H bond scission
to produce syngas (CO and H 2 ) via reforming reaction.
Selective hydrodeoxygenation (HDO)/deoxygenation is one of the pivotal reactions to
remove excess oxygen from bio-oils to produce transportation fuels without reducing the carbon
chain length.3 Reforming reaction, on the other hand, is an attractive alternative way to produce
hydrogen from renewable biomass, instead of the current production method from natural gas
and petroleum.4 Typical HDO and reforming catalysts include precious metal based catalysts
such as Pt and Pd but the use of such catalysts in large-scale biomass conversion is hindered by
high costs and scarcity of precious metals. Cost effective non-precious metal catalysts, however,
suffer from low activity and rapid deactivation. The search for enhanced catalytic activity of
non-precious metal requires an understanding of reaction pathways of oxygenates on metal
surfaces.
In this study, we investigate the reaction of propanal on Mo(110) and monolayer (ML)
Co/Mo(110) surfaces, and compare with that of 1-propanol. Briefly summarizing our results,
DFT results show that the binding energies of oxygen and propanal on Mo(110) can be reduced
by the deposition of surface monolayer of Co, suggesting potentially different reaction pathways
between the two surfaces. Previously it has been reported that a stronger Mo‒O binding energy
results in breaking the C‒O bond due to a stronger thermodynamic driving force.5,6 TPD results
confirm that the major reaction pathways of propanal show that Mo(110) selectively cleaves the
C=O bond to produce propene and has the highest activity for deoxygenation while Co/Mo(110)
shows an enhanced activity in the C‒C and C‒H bond scission to produce syngas. HREELS
experiments were performed to determine the surface reaction intermediates. The results show
that the decomposition of C‒C‒C and C=O on Mo(110) does not start until 400 K, whereas on
the bimetallic surfaces the decomposition of C‒C‒C bond has already completed by 400 K.
Parallel study of 1-propanol on Mo(110) and ML Co/Mo(110) also reveals similar reaction
mechanisms. Our results demonstrate the feasibility of controlling reaction pathways of small
oxygenates which can be extended for more complex biomass-derived oxygenate platform
molecules.
1. Medlin, J. W., ACS Catal. 2011, 1, 1284-1297.
2. Mavrikakis, M.; Barteau, M. A., J. Mol. Catal. A: Chem. 1998, 131, 135-147.
3. Gosselink, R. W.; Hollak, S. A. W.; Chang, S.-W.; van Haveren, J.; de Jong, K. P.; Bitter, J. H.; van Es, D. S.,
ChemSusChem 2013, 6, 1576-1594.
4. Alonso, D. M.; Wettstein, S. G.; Dumesic, J. A., Chem. Soc. Rev. 2012, 41, 8075-8098.
5. Chen, D. A.; Friend, C. M., J. Phys. Chem. 1996, 100, 17640-17647.
6. Yu, W.; Salciccioli, M.; Xiong, K.; Barteau, M. A.; Vlachos, D. G.; Chen, J. G., ACS Catal. 2014, 4, 1409-1418.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Molecular Plasticity of Single Cells in Disease Pathology
James Park
Advisor: Babatunde Ogunnaike, James Schwaber, Rajanikanth Vadigepalli
Committee Members: David Colby, Abhyudai Singh
Recent advances in “-omics” technologies have supported mounting experimental evidence
showing a significant amount of plasticity and heterogeneity across single cells within a defined
phenotype, particularly within post-mitotic neurons of the brain. Heterogeneity exists across
multiple measures of neuronal state, ranging from mRNA expression levels to electrophysiological
activity. Unfortunately, variability within a developed cell-type confounds our understanding of
how a neuron-type contributes to brain function. While many of the genetic programs that underlie
developmental plasticity have been elucidated, the underlying gene regulatory networks driving
cellular plasticity and variability post-development are not understood clearly. Therefore
determining the underlying regulatory networks that drive neuronal state contributing to
heterogeneity and plasticity would provide insight into how such variability contributes to
neurogenic control of physiological systems in normal and disease pathologies.
In order to determine the molecular framework constraining plasticity and variability within postmitotic neurons, it is important to understand the molecular mechanisms underlying the state and
function of individual neurons. To this end, we aim to identify the gene regulatory networks
underlying neuronal variability and plasticity. In order to elucidate these mechanisms, we
developed a high-dimensional gene expression dataset consisting of hundreds of individual
neurons belonging to a neuroanatomical phenotype. We collected single neurons from the nucleus
tractus solitarius (NTS – a brainstem nucleus involved in autonomic control of blood pressure)
from baseline normotensive and hypertensive rats. Using several multivariate analytical methods,
we identified emergent functional subtypes of NTS neurons that align with distinct synaptic input
types related to blood pressure changes and higher order cardiovascular demands. We
subsequently developed a fuzzy logic-based modeling approach that draws upon the variability
observed in single-cell transcription to identify the regulatory networks driving the transcriptional
behavior of these subtypes. Our modeling simulations suggest that the heterogeneity and plasticity
observed within a neuroanatomical phenotype can be viewed as a mixture of regulatory network
phenotypes responding to a range of inputs related to physiological state.
Based on these results we will extend our experimental and analytical approaches to investigate
further the role NTS neuronal plasticity has in autonomic control under conditions of homeostatic
dysregulation such as low vagal tone of the heart and alcohol withdrawal progression. The insights
gained form these studies will allow us to develop model-driven hypotheses on how to affect these
regulatory networks to potentially rescue or prevent the maladaptation of neurons associated with
disease progression. In this presentation, current progress in understanding the functional
significance of the transcriptional variability observed in NTS neurons and the underlying gene
regulatory networks driving this variability will be discussed.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Mechanistic Insights into the Selective Conversion of CO2 to CO on Precious and NonPrecious Metal Electrocatalysts
Jonathan Rosen
Advisor: Feng Jiao
Committee Members: Douglas Buttrey and Raul Lobo
Increased atmospheric emissions of CO2 from the burning of fossil fuels has been cited as
one of the primary causes of climate change.1 In order to reduce CO2 emissions several solutions
have been proposed, such as the increased use of carbon neutral fuels as well as CO2
sequestration and conversion technologies. Solar fuels or artificial photosynthetic devices are a
promising alternative due to their potential to convert sunlight and highly undesirable CO2 into a
renewable source of liquid fuels such as methane, methanol, and hydrocarbons. Important
components of these technologies are the water splitting and CO2 conversion catalysts, which
have significant effects on the rate of reaction and energy efficiency. A common issue currently
affecting state of the art catalysts is the significant energy penalty (i.e. overpotential) required to
drive these reactions. Therefore, developing efficient catalysts able to operate with smaller
overpotential is crucial to the success of solar fuel technologies. Past work in our lab has focused
on developing highly active and inexpensive and transition metal water splitting catalysts.23 Of
equal importance though, is the development of efficient CO2 reduction catalysts.
Recently our lab has designed a highly active nanoporous Ag electrocatalyst with the
ability to reduce CO2 selectively towards CO with some of the best rates (i.e. currents) reported
to date with dramatically reduced overpotential.4 The improved intrinsic activity is a result of
higher CO2 reduction activity on stepped surfaces. To further confirm this theory other
nanostructured Ag catalysts such as nanoparticles were examined and also showed increased
current densities and CO selectivity due to their higher abundance of stepped sites. Electrokinetic
insight from Tafel analysis and Density Functional Theory has shown a different rate-limiting
mechanism on nanostructured silver catalysts compared to bulk, requiring significantly reduced
overpotentials needed to drive the reaction.5
Due to the rarity and cost of Ag, developing other catalysts using less noble transition
metals such as Zn is also of significant interest. Electrochemical deposition of metals has shown
promise as a method of synthesizing highly active nanostructured CO2 reduction catalysts.
Taking advantage of this technique, we were able to develop an electrodeposited Zn catalyst with
dendrite morphology by tuning conditions such as the rate of deposition. The electrodeposited Zn
catalyst shows the ability to selectively reduce CO2 at rates around an order of magnitude higher
than bulk Zn with great long term stability. It is likely that the high surface area and defect sites
formed in the electrochemical deposition of Zn are the source of the improved CO2 reduction
activity and tolerance to the reaction conditions. In-situ X-ray Absorption Spectroscopy was able
to characterize the behavior of the Zn catalyst during CO2 electrolysis, giving further insight into
the effect of oxidation state and coordination on CO2 reduction activity.
(1)
(2)
(3)
(4)
(5)
Lewis, N. S.; Nocera, D. G. Proc. Natl. Acad. Sci. 2006, 103 , 15729–15735.
Rosen, J.; Hutchings, G. S.; Jiao, F. J. Catal. 2014, 310, 2–9.
Rosen, J.; Hutchings, G. S.; Jiao, F. J. Am. Chem. Soc. 2013, 135, 4516–4521.
Lu, Q.; Rosen, J.; Zhou, Y.; Hutchings, G. S.; Kimmel, Y. C.; Chen, J. G.; Jiao, F. Nat Commun 2014, 5, 3242.
Rosen, J.; Hutchings, G. S.; Lu, Q.; Rivera, S.; Zhou, Y.; Vlachos, D.; Jiao, F. (In Review)
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Tunable Hydrogels to Understand the Role of the Microenvironment in Regulating Breast
Cancer Dormancy and Recurrence
Lisa A. Sawicki
Advisor: April M. Kloxin
Committee Members: Kelvin H. Lee, Wilfred Chen, Millicent O. Sullivan
Breast cancer reoccurs in approximately 20 percent of all patients between 5 and 10 years after
successful treatment of the primary tumor.1 Most of these recurrences occur at a metastatic site
and are hypothesized to arise from tumor cells that have reactivated after a long period of
dormancy. Remodeling of the extracellular matrix (ECM) at these sites over time is thought to
trigger the release of the tumor cells from dormancy.2 Two-dimensional (2D) and threedimensional (3D) in vitro culture models have been developed to recreate some of the
interactions between cancer cells and their microenvironment.3,4 Lack of mechanical property
control and differences between biochemical composition of these model systems and the native
ECM make it challenging to identify key ECM signals that promote dormancy or activation.
To address this need, we are designing a hydrogel-based 3D culture platform to mimic critical
mechanical and biochemical properties of different metastatic site tissues where breast cancer
dormancy most often occurs, including the bone marrow, liver, and lung. With this approach, we
aim to identify cues that play a role in dormancy and reactivation of tumor cells toward the
identification of new therapeutic targets to maintain dormancy and prevent recurrence.
Specifically, poly(ethylene glycol)(PEG)-based hydrogels have been polymerized by a radicallyinitiated thiol−ene chemistry using PEG-4-thiol, and peptides modified with alloxycarbonylprotected lysine residues to supply a biologically-orthogonal reactive functional group (−ene) for
the formation of a step-growth hydrogel with ideal network structure.7 Hydrogels formed within
5 minutes after the application of cytocompatible doses of UV light (10 mW/cm2, 365 nm) in the
presence of the photoinitiator lithium acylphosphinate. Mechanical properties of the hydrogels
were measured, and the elastic moduli of soft metastatic site tissues were achieved (Young’s
modulus (E) ~ 0.5-5 kPa). Further, biomimetic peptides have been spatially patterned within the
matrix to mimic the nonhomogeneous in vivo microenvironment. These tunable hydrogels are
being used to investigate matrix compositions that promote cancer dormancy or activation. We
have cultured human breast cancer cells (MCF7s) on stiff substrates and quantified activation
and dormancy by immunostaining for a marker of proliferation (Ki-67), establishing controls in
2D culture. Finally, moving toward 3D culture, MCF7s were encapsulated within hydrogels
containing various combinations of proteins and integrin binding peptides to determine critical
cues present in the ECM that regulate activation and dormancy.
1
2
3
4
5
6
A Brewster, et al. J Natl Cancer Inst. 2008, 100, 1179-1183.
J Townson, et al. Cell Cycle. 2006, 5, 1744-1750.
J Barrios, et al. Cancer Microenviron. 2009, 2, 33-47.
D Barkan, et al. Cancer Res. 2008, 68, 6241-6250.
M Lutolf, et al. PNAS. 2003, 100, 5413-5418.
L Sawicki, et al. Biomaterials Science 2014, 2, 1612-1626.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
Engineering- and Systems-based Approaches Enable Analysis of Proteins Involved in
Chlorobaculum tepidum Sulfur Metabolism
Amalie Tuerk
Advisor: Kelvin Lee
Committee Members: Wilfred Chen, Thomas Hanson, April Kloxin, Eleftherios Papoutsakis
Microbes that synthesize or degrade insoluble mineral surfaces play key roles in environmental
nutrient cycling and catalyze certain industrial processes. In particular, microbes that interact
with sulfur-containing minerals have applications in biomining and in the remediation of
hydrogen sulfide-containing biogas and wastewater streams. Some sulfur oxidizing bacteria,
such as the phototroph Chlorobaculum tepidum, perform both mineral synthesis and degradation.
Cba. tepidum produces extracellular, insoluble zero-valent sulfur globules (S0) as an intermediate
of sulfide and thiosulfate oxidation, subsequently oxidizing S0 to sulfate. Even though this
process is an obligate consequence of its energy metabolism, the mechanisms of S0 synthesis and
degradation are poorly understood.
This research employs engineering- and systems-based approaches to study S0 metabolism in
Cba. tepidum. We are particularly interested in identifying proteins involved in S0 synthesis and
degradation and proteins at the microbe-S0 interface to provide insight into the mechanisms of
cell-mineral interactions.
Variable growth of Cba. tepidum poses challenges to detailed studies of this organism. We
developed standardized culture methods to enable reproducible of growth of Cba. tepidum by
reducing variability in inoculum preparation, light intensity, and oxygen exposure in the absence
of sulfide. These improvements allowed, for the first time, the validation of biomass quantitation
methods for Cba. tepidum grown under a range of conditions. In addition to providing an
improved basis for assessing growth yields on sulfur electron donors, these studies provided
novel insights into the physiology of Cba. tepidum under energy-rich and energy-poor growth
conditions.
A proteomic evaluation of S0 globules produced by Cba. tepidum has identified two conserved
proteins of unknown function likely involved in S0 metabolism. To characterize their biological
roles, these proteins are targets for analysis by ongoing deletion mutagenesis experiments. More
extensive proteomic analyses of Cba. tepidum grown under S0-producing versus S0-degrading
conditions will enable a quantitative analysis of proteins involved in S0 metabolism and
validation of our initial observations.
------------------------------------------------------------------------------------- ------------------Winter Research Review 2015
A CMP-based method for achieving Controlled, Cell-Responsive Delivery of DNA
Morgan A. Urello
Advisor: Dr. Millicent O. Sullivan and Dr. Kristi L. Kiick
Committee Members: Dr. David Colby and Dr. April Kloxin
Collagen-based delivery systems offer appealing advantages in regenerative medicine. The most
abundant of mammalian proteins, collagens are often employed as tissue scaffolds or 3D culture
materials because of their innate biocompatibility and bioactivity and because of their key
structural role in a variety of tissues.1 These properties also make them promising biomaterials
for the controlled delivery of DNA-based therapeutics. Accordingly, a variety of collagen
modification techniques have been developed for the purpose of retaining and controlling the
release of DNA. While a majority of these methods are chemical-based, a new biomimetic
strategy to non-covalently modify collagen scaffolds with collagen mimetic peptides (CMPs)
boasts compelling advantages. Specifically, thermal annealing mediates strand exchange of short
CMPs into the triple-helical collagen structure and can enable robust modification of collagen
scaffolds with growth factors, nanoparticles, and polymers, as well as obviate the need for
chemical modifications that may compromise the bioactivity of the scaffold. Highly versatile, the
strength and duration of the CMP-collagen interaction can be tailored via variation of the amino
acid composition and molecular weight of the CMP.2
The goal of this project is to utilize the natural properties of collagen coupled with the synthetic
nature of CMPs to engineer a high efficiency, non-viral DNA delivery system. While generally
regarded as safer than viral DNA therapies, non-viral therapies do not have the innate
transfection efficiencies that viral therapies have evolved. To increase the viability of non-viral
delivery approaches, we propose a versatile CMP-collagen-based method for achieving
localized, controlled release of non-viral DNA vehicles from collagen that exploits the natural
process of collagen remodeling to improved transfection efficiency. During this process,
collagen is fragmented and internalized into cells via caveolar-endocytosis, a pathway linked to
the initiation of high efficiency gene expression.3 Mimicking the delivery of many viruses, our
goal is to hijack this collagen repair mechanism, which occurs in excess in many targeted
delivery sites such as tumors, chronic wounds, and bone abnormalities 2, to achieve efficient
delivery. In our work, we have shown that both the CMP sequence and the density of CMPs on
DNA-polymer ”polyplexes,” can be used to tailor the release of DNA from 2-D collagen films
and 3-D collagen gels, for over two weeks and a month, respectively. We have also demonstrated
that CMP-modified polyplexes in collagen have considerably enhanced stability under
physiological conditions, as compared to non-modified polyplexes, and these CMP-modified
polyplexes are released in a cell-responsive manner. Our results strongly suggest that the
observed improvement in transfection efficiency of CMP-modified polyplexes is due in part to
co-internalization with collagen fragments as well as an increase in uptake by caveolar
endocytosis. This study is not only the first to utilize CMP-based modification of collagen to
deliver DNA-based therapeutics, but also one of the first to thoroughly examine the potential of
collagen remodeling in non-viral delivery. Our results suggest that this method may be used
more broadly to create tunable, collagen-based systems as well as other DNA delivery systems
specifically tailored for improved delivery to tumors, chronic wounds, and other sites in which
excessive collagen remodeling is occurring.
1
2
3
K. Stenzel, et al. Annual Review of Biophysics and Bioengineering, 1974, 3, 231-53.
Y. Li., et al., Proceedings of the National Academy of Sciences, 2012, 109, 14767-4772.
M. Reilly, et al., Mol. Pharmaceutics, 2012, 9, 2031-1040.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
High-Performance Dealloyed PtCu/CuNW Oxygen Reduction Reaction
Catalyst for Proton Exchange Membrane Fuel Cells
Jarrid A. Wittkopf
Advisor: Yushan Yan
Committee Members: Feng Jiao and Dionisios Vlachos
One major barrier to fuel cell commercialization is the high cost of oxygen reduction reaction
(ORR) catalysts. Current catalysts are predominantly supported Pt nanoparticles. These
nanoparticles show high surface area but low specific activity and durability. A transition to
unsupported catalysts possessing an extended surface should improve both specific activity and
durability and in turn, cost-effectiveness when high surface area can be achieved. Platinumcoated copper nanowires (Pt/CuNW) exemplify these advantages. In this study, post-synthetic
processing is used to further improve the performance of Pt/CuNW catalyst. Specifically,
annealing followed by electrochemical dealloying enhances activity through geometric lattice
tuning. The resultant bimetallic PtCu/CuNW catalyst yields specific and mass activities (SA and
MA) of 2.65 mA cmPt-2 and 1.24 A mgPt-1, surpassing the respective DOE benchmarks of 0.72
mA cm-2 and 0.44 A mgPt-1. PtCu/CuNWs demonstrate enhanced durability over Pt nanoparticle
catalysts by maintaining 64.1 % of its active surface area after 30,000 cycles between 0.6 - 1.1
vs. RHE at a scan rate of 50 mV s-1 in Ar saturated 0.1 M HClO4. Post durability PtCu/CuNWs
outperformed the DOE benchmarks with a SA and MA of 1.50 mA cmPt-2 and 0.477 A mgPt-1.
-------------------------------------------------------------------------------------------------------Winter Research Review 2015
In-Situ Kinetic Studies of the Hydrogen Oxidation Reaction in Hydroxide Exchange
Membrane Fuel Cells
Mariah Woodroof
Advisor: Yushan Yan
Committee Members: Feng Jiao, Abraham Lenhoff, Raul Lobo, Richard Wool
Hydrogen fuel cells convert chemical potential directly into electrical energy by separating the
hydrogen oxidation (HOR) and oxygen reduction reactions with an ion exchange membrane
(IEM). Since the HOR activity is so sensitive to pH changes, measuring its kinetics has become a
major focus in electrochemistry. The exchange current density (i o ) is a parameter used to
quantify the HOR activity and is traditionally measured by fitting the Butler-Volmer equation to
the HOR kinetic current in liquid electrolyte. However, the kinetics of the HOR in an acid
system are too fast and therefore masked by the inherent diffusion limitations in liquid
electrolyte. To eliminate these mass transfer limitations, a hydrogen pump cell can be used to
measure in-situ HOR kinetics in a solid electrolyte IEM system. The HOR kinetics on platinum
have previously been studied in this system using a Nafion® proton exchange membrane (PEM)
and ionomer.
Although slower HOR kinetics in an alkaline system allow for the calculation of i o in liquid
base, there has been no reported measurements of the in-situ HOR kinetics in a solid electrolyte
hydroxide exchange membrane (HEM). The goal of this work is to determine if the HOR
kinetics in liquid base mirror the kinetics found in a HEM fuel cell. The HOR activity was
calculated for a platinum catalyst interfaced with a commercial HEM and its respective ionomer
using a H 2 - pump. When the Butler-Volmer equation was fit to the H 2 -pump HOR polarization
curve, the in-situ i o was found to be slightly higher than the i o measured in liquid base. To
investigate the difference in the i o values, voltage shifts of the hydrogen desorption peaks
between the in-situ and liquid base cyclic voltammagrams were further examined. Future work
will involve using the H 2 -pump to measure i o for non-precious metal catalysts that can be used
in HEM fuel cells and determine if their kinetics in a fuel cell differ from their previously
measured kinetics in liquid base electrolyte.
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Greater Cincinnati Foundation
Henley Foundation
Norman N. & Gale R. Hochgraf Charitable Foundation
IBM International Foundation
International Fine Particle Research Institute
Johnson & Johnson Family of Cos.
Medtronic Foundation
Merck Company Foundation
Merck Sharp & Dohme
National Fuel Gas Company Foundation
Novellus Systems, Inc.
P&G Fund of The Greater Cincinnati Foundation
Schwab Charitable Fund
Shell Oil Company Foundation
The Pfizer Foundation, Inc.
United Technologies Corporation
Xerox Corporation U.S.A.
Equal Opportunity Employer
The University of Delaware is an equal opportunity/affirmative action employer. For the
University’s complete non-discrimination statement, please visit http://www.udel.edu/
aboutus/legalnotices.html